Anemonefish and anemones are one of the most iconic symbiotic relationships that occur globally. Despite decades of study, there are still significant gaps in our knowledge of the evolution and persistence of anemonefish and how they live and thrive within their venomous hosts. In this chapter, we will explore the mechanism of toxin resistance in the establishment of this relationship and will discuss the current hypotheses posed to explain how the anemonefish mucus layer acts to protect the anemonefish from anemone venom. Research into anemonefish and their anemone home is increasingly employing the use of omics technologies, such as genomics and metagenomics. We will explore how utilizing these technologies has helped us deepen our understanding of the anemonefish and anemone symbiosis, as well as the future applications of omics techniques that may help us finally uncover the mechanisms behind this fascinating relationship.